Our customers in the animal health and human pharmaceutical industries constantly improve the efficiency of their manufacturing processes. One result of this is the effort to get to even higher cell densities. In the Phase I studies and in subsequent experiments performed using corporate funding we demonstrated that (1) cell densities can be dramatically increased by utilizing very small beads (38-63 microM), (2) the high cell densities were achieved because of rapid cell attachment, concomitant aggregation and cell growth and (3) the cells remained metabolically active producing biologicals. Seifert reported intentional aggregation, which is akin to forming macroporous microcarriers in situ. He showed that cells gather in the low-shear interstitial voids because nutrient flow was sufficient. Our experimental activities will address the following aims: 1. To identify the critical process engineering variables that determine small microcarrier-cell culture aggregate performance in stirred tank bioreactors. 2. To optimize high density growth in small microcarrier-cell culture aggregate systems using production of commercially important biologicals as the endpoint. 3. To demonstrate successful cell growth in high density, aggregate microcarrier cell culture at 5-liter scale. PROPOSED COMMERCIAL APPLICATION: SoloHill has grown to a position where it supplies about 25% of the worldwide microcarrier market with two products developed under earlier NCI grants. To have captured this market from a large Swedish firm is strong testimony to the importance of introducing innovative products. This potential new product, Aggregate Microcarriers, can fulfil the promise of macroporous microcarriers (ultrahigh surface area with low shear regions and can be formed in situ). When successful this innovative product will allow SoloHill to directly compete for the growing markets along the Pacific Rim.